Page 214 - Medicine and Surgery

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210 Chapter 5: Hepatic, biliary and pancreatic systems

Investigations urine and an enlarged liver. Occasionally, the individual
Endoscopic retrograde cholangiopancreatography isasymptomaticuntiladulthood,whentheypresentwith
(ERCP) shows a beaded appearance of the large bile cirrhosis.
ducts. Liver biopsy is diagnostic demonstrating concen-
tric, (onion-skin) fibrosis around medium-sized bile Investigations
ducts, including those in portal tracts. Small bile ducts Liver function tests are abnormal. Liver biopsy shows
scar and vanish. variable histology including hepatocellular necrosis, in-
flammation, fibrosis and cirrhosis. α 1 antitrypsin levels
Management can be measured and are low.
Corticosteroids, azathiporine and methotrexate have
been tried, but have no proven benefit. Drainage is usu-
Management
ally ineffective. Liver transplantation is used in advanced
Supportive,patientsmustnotsmoke,end-stageliverfail-
cases.
ure may require liver transplantation.
Prognosis
Slowly progresses to chronic liver disease with risk of ful- Hereditary haemochromatosis
minant hepatic failure, cholangiocarcinoma and hepa-
tocellular carcinoma. There is an increased risk of colon Definition
cancer. Inherited disorder resulting in abnormal accumulation
of iron in the body.
α 1 Antitrypsin deficiency
Incidence/prevalence
Definition Homozygous mutation 1 in 350, clinical disease rare.
Inherited cause of chronic liver disease and panacinar
emphysema. Age
Clinical disease; most common in middle age.
Aetiology
The gene for α 1 antitrypsin (Pi, for Protease Inhibitor)
Sex
is found on chromosome 14. It has more than 30 differ-
Clinical disease, M > F.
ent alleles which are defined according to their motility
on electrophoretic gel. The normal phenotype is desig-
nated PiMM. Z is the most abnormal allele, it encodes Aetiology
Hereditary haemochromatosis is inherited in an autoso-
for a defective protein which cannot be excreted from
mal recessive manner. The carrier frequency is 1 in 10.
hepatocytes.
The gene (HFE) is located on the short arm of chro-
mosome 6, closely linked to HLA A3. The commonest
Pathophysiology
mutation is a cysteine-to-tyrosine substitution at amino
α 1 antitrypsin is an extracellular inhibitor of neutrophil
acid 282 (C282Y). Although 80–90% of patients with
elastase. In its absence, damage to cells is not controlled.
Individuals who have a PiMZ phenotype have an in- hereditary haemochromatosis are homozygous for the
creased risk of developing emphysema. Cigarette smoke C282Y mutation, 75–99% of homozygotes are clinically
probably contributes to this by inhibiting any function- disease free.
ing antitrypsin which is present. Those with a ZZ phe-
notype develop emphysema and cirrhosis. Pathophysiology
The mechanism by which HFE mutation causes disease
Clinical features is unclear. It is thought that there is a gradual accumula-
ZZ homozygotes usually present in the first year of life, tion of iron over decades. Women accumulate less iron
withsymptomsofneonatalhepatitis,i.e.palestools,dark due to menstrual losses and therefore present later. Iron